Norman D. Grace

Harvard University, Cambridge, Massachusetts, United States

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Publications (58)568.79 Total impact

  • Raffi Karagozian · Norman D Grace · Amir A Qamar
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    ABSTRACT: Abnormal hematological indices (HI) are common in cirrhosis from hepatitis C virus (HCV). Eradication of HCV may ameliorate these abnormalities. The objectives of the current study were to assess whether HI improve with HCV eradication and whether they can predict prognosis in patients with cirrhosis during and after completion of antiviral therapy. A retrospective cohort study of 153 patients with HCV cirrhosis treated with Peg-interferon and ribavirin was conducted. The primary endpoint was improvement in HI after successful antiviral therapy. The secondary outcome was clinical decompensation during and after completion of antiviral therapy and association with HI. A repeated measures 2-way ANOVA was performed to compare means. Multivariate analysis was used to identify predictors of clinical decompensation. One hundred fifty three patients met study criteria. The rate of sustained virological rate was 26%. Median follow-up was 55 months. Platelet and WBC counts improved with HCV eradication compared to those in whom treatment was unsuccessful (p < 0.05). On univariate analysis, the presence of thrombocytopenia was associated clinical decompensation prior to, on treatment and after completion of therapy. Thrombocytopenia (OR 14.8, p-value <0.001) after completing treatment predicted clinical decompensation when controlled for albumin, MELD and age in multivariate analysis at 6 months after completion of therapy. Platelet and leukocyte counts improve in patients with cirrhosis who respond to antiviral therapy against HCV. The presence of thrombocytopenia predicts decompensation on treatment and after completion of therapy.
    Acta gastro-enterologica Belgica 12/2014; 77(4):425-32. · 0.91 Impact Factor
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    ABSTRACT: Background: Mortality from ST elevation myocardial infarction (STEMI) is decreasing nationwide, but no report to date examined STEMI mortality among patients with cirrhosis. Goals: Determine mortality rates and investigate possible disparities in cardiovascular interventions for patients with and without cirrhosis admitted with STEMI across a decade using a national database. Study: We included all urgent/emergent admissions with STEMI to acute care hospitals across the United States in 1999 and 2009. Exclusion criteria were age less than 18 years or prior liver transplantation. Confounders were accounted for using multivariable regression analyses. Results: A total of 325,857 and 182,491 patients with STEMI were included in 1999 and 2009, respectively, 741 and 541 of whom had cirrhosis, respectively. In-hospital mortality rate was 31% and 11% for patients with and without cirrhosis in 1999, and 17% and 9% in 2009. The adjusted mortality odds ratio was 2.54 (1.52 to 4.24) in 1999 and 1.45 (0.73 to 2.86) in 2009. Stent placement rate was 11% and 26% for patients with and without cirrhosis in 1999, and increased to 47% and 61% in 2009, respectively. Thrombolytic medication injection rate was 3% and 10% for patients with and without cirrhosis in 1999, and 0% and 2% in 2009, respectively. Coronary artery bypass graft surgery rate was 3% and 9% for patients with and without cirrhosis in 1999, and was 6% and 7% in 2009, respectively. Conclusions: STEMI mortality in patients with cirrhosis is higher compared with patients without cirrhosis. However, this mortality difference declined from 1999 to 2009, likely because of higher coronary artery stent utilization for patients with cirrhosis. Copyright
    Journal of Clinical Gastroenterology 10/2014; Publish Ahead of Print(9). DOI:10.1097/MCG.0000000000000251 · 3.50 Impact Factor
  • Sonal Kumar · Norman D Grace · Amir A Qamar
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    ABSTRACT: Statins reduce cardiovascular risk. Patients with cirrhosis have decreased hepatic clearance of statins and potentially increased risk for complications. No studies assess mortality in patients with biopsy-confirmed cirrhosis. Compare mortality in patients with cirrhosis on statins to those not on statins. A retrospective cohort study evaluated patients from 1988 to 2011 at Partners Healthcare Hospitals. The Partners Research Patient Data Registry identified patients with biopsy-proven cirrhosis on statins at biopsy and at least 3 months following. Controls were matched 1:2 by age, gender and Child-Pugh class. Decompensation was defined as ascites, jaundice/bilirubin > 2.5 mg/dL, and/or hepatic encephalopathy or variceal hemorrhage. Primary outcome was mortality. Secondary outcome was decompensation in baseline-compensated patients. Chi-square and two-way ANOVA testing compared groups. Cox proportional hazards models for mortality controlled for age, Child-Pugh class, diabetes, coronary artery disease, non-alcoholic steatohepatitis and hepatocellular carcinoma. Kaplan-Meier curves graphed mortality. Eighty-one statin users and 162 controls were included. Median follow-up: 36 months in statin users and 30 months in controls. 70.4 % of patients were Child-Pugh A. Model for End-Stage Liver Disease (MELD), albumin, varices and beta-blocker use were not significantly different between groups. Statin users had lower mortality on multivariate analysis (HR 0.53, p = 0.01), and Child-Pugh A patients had longer survival on Kaplan-Meier analysis. Cox multivariate analysis for decompensation showed lower risk of decompensation with statins while increased decompensation with low albumin, high MELD score and beta-blocker use. In patients with cirrhosis, statin therapy is not associated with increased mortality and may delay decompensation.
    Digestive Diseases and Sciences 05/2014; 59(8). DOI:10.1007/s10620-014-3179-2 · 2.61 Impact Factor
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    ABSTRACT: Unlabelled: The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had cirrhosis and portal hypertension but did not have GEV. A total of 90 patients who had baseline day-1 sera available were enrolled in the present study. The objective of this study was to determine whether inflammatory biomarkers in conjunction with clinical parameters could be used to develop a predictive paradigm for HVPG. The correlations between HVPG and interleukin (IL)-1β (P=0.0052); IL-1R-α (P=0.0085); Fas-R (P=0.0354), and serum VCAM-1 (P=0.0007) were highly significant. By using multivariate logistic regression analysis and selected parameters (transforming growth factor beta [TGFβ]; heat shock protein [HSP]-70; at-risk alcohol use; and Child class B) we could exclude HVPG ≥ 12 mmHg with 86% accuracy (95% confidence interval [CI]: 67.78 to 96.16%) and the sensitivity was 87.01% (95% CI: 69.68 to 96.34%). Therefore, the composite test could identify 86% of compensated cirrhosis patients with HVPG below 12 mmHg and prevent unnecessary esophagogastroduodenoscopy with its associated morbidity and costs in these patients. Our diagnostic test was not efficient in predicting HVPG ≥ 12 mmHg. Conclusion: A blood test for HVPG could be performed in cirrhosis patients to prevent unnecessary esophagogastroduodenoscopy.
    Hepatology 03/2014; 59(3). DOI:10.1002/hep.26755 · 11.06 Impact Factor
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    ABSTRACT: It remains unclear whether a long-acting preparation of octreotide (Sandostatin LAR) can be safely used for portal hypertension in patients with compensated cirrhosis. To determine the safety and efficacy of LAR among patients with Child Pugh Class A or B cirrhosis and small oesophageal varices. A randomised, double-blind, placebo-controlled study was conducted in 39 patients with cirrhosis and small oesophageal varices. Safety was based on frequency and severity of adverse events. Efficacy was determined by hepatic vein pressure gradient (HVPG) measured at baseline and day 84 following administration of LAR 10 mg (n = 15), 30 mg (n = 10) or saline (n = 14). Fasting and postprandial portal blood flow (PBF), superior mesenteric artery pulsatility index (SMA-PI), glucagon and octreotide levels were measured. An intention-to-treat analysis was performed. Four patients in the LAR 30 group (40%) withdrew from the study due to serious adverse events. No patient in the LAR 10 or control group had serious adverse events. There was no statistically significant decrease between HVPG at day 84 and baseline with LAR 30 mg (11.8 ± 2.3 mmHg vs. 14.1 ± 3.2), LAR 10 mg (15.3 ± 4.8 mmHg vs. 15.1 ± 3.8), or saline (13.3 ± 3.8 mmHg vs. 15.1 ± 4.3) (P = 0.26). Neither PBF, SMA-PI nor plasma glucagon levels were significantly decreased from baseline (P = 0.56). The absence of significant haemodynamic benefit, as well as the high frequency of severe adverse events associated with use of LAR, do not support the use of this agent in the treatment of portal hypertension.
    Alimentary Pharmacology & Therapeutics 03/2012; 35(8):904-12. DOI:10.1111/j.1365-2036.2012.05050.x · 5.73 Impact Factor
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    ABSTRACT: Obesity is associated with an aggressive course in chronic viral hepatitis; however, its impact in the development of clinical decompensation (CD) in patients with established cirrhosis is uncertain. We evaluated the role of obesity, in relationship to other recognized predictors, in the development of CD in patients with compensated cirrhosis. The study population, a subset of patients included in a randomized trial of beta-blockers in the prevention of varices in whom data on body mass index (BMI) was available, consisted of 161 patients with compensated cirrhosis. Laboratory tests and portal pressure (assessed by the hepatic venous pressure gradient or HVPG) were assessed on inclusion. Patients were followed until CD (ascites, hepatic encephalopathy, or variceal hemorrhage), or until September 2002. Altogether, 29% had a normal BMI, 40% were overweight, and 30% were obese. In a median follow-up of 59 months, CD occurred in 48/161 (30%) patients with an increasingly higher rate according to BMI group (15% in those with normal BMI; 31% in overweight; 43% in obese patients, P=0.011). The actuarial probability of developing CD was significantly higher in the abnormal BMI groups (P=0.022). In a multivariate model that included parameters previously identified as being predictive of CD (HVPG, albumin, Mayo endstage liver disease score), etiology, and treatment group, BMI (hazard ration 1.06; 95% confidence interval 1.01-1.12), P=0.02] was an independent predictor of decompensation, together with HVPG and albumin. CONCLUSION: Obesity has a deleterious effect on the natural history of compensated cirrhosis of all etiologies, independent of portal pressure and liver function. Weight reduction may be a valuable therapeutic measure in this patient population.
    Hepatology 08/2011; 54(2):555-61. DOI:10.1002/hep.24418 · 11.06 Impact Factor
  • Norman D Grace
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2011; 9(7):536-8. DOI:10.1016/j.cgh.2011.04.013 · 7.90 Impact Factor
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    ABSTRACT: This chapter contains sections titled: Beta-blockers alone or combined with other drugsEndoscopic therapy: endoscopic variceal ligation or combined with other endoscopic proceduresDrugs alone or with endoscopic variceal ligation?Endoscopic variceal ligation alone or with drugs?Transjugular intrahepatic portosystemic shunt versus endoscopic treatmentRescue therapy: always TIPS? Treatment of poor candidates for TIPSSecondary prophylaxis of variceal bleeding:Role of surgeryThe role of HVPG monitoring in secondary prophylaxisReferencesTime to start secondary prophylaxis
    Portal Hypertension V, 11/2010: pages 119-131; , ISBN: 9781444334494
  • Gastroenterology 05/2010; 138(5). DOI:10.1016/S0016-5085(10)63764-X · 16.72 Impact Factor
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    A A Qamar · N D Grace
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    ABSTRACT: Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 07/2009; 23(6):441-5. · 1.98 Impact Factor
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    ABSTRACT: A total of 213 patients with compensated cirrhosis, portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices. Predictors of the development of hepatocellular carcinoma (HCC), including hepatic venous pressure gradient (HVPG) were analyzed. Baseline laboratory tests, ultrasound and HVPG measurements were performed. Patients were followed prospectively every three months until development of varices or variceal bleeding or end of the study in 09/02. The endpoint was HCC development according to standard diagnostic criteria. Univariate and multivariate Cox regression models were developed to identify predictors of HCC. In a median follow-up of 58 months 26/213 (12.2%) patients developed HCC. Eight patients were transplanted and 28 patients died without HCC. Twenty-one (84%) HCC developed in patients with HCV. On multivariate analysis HVPG (HR 1.18; 95%CI 1.08-1.29), albumin (HR 0.34; 95%CI 0.14-0.83) and viral etiology (HR 4.59; 95%CI 1.51-13.92) were independent predictors of HCC development. ROC curves identified 10 mmHg of HVPG as the best cut-off; those who had an HVPG above this value had a 6-fold increase in the HCC incidence. Portal hypertension is an independent predictor of HCC development. An HVPG >10 mmHg is associated with a 6-fold increase of HCC risk.
    Journal of Hepatology 03/2009; 50(5):923-8. DOI:10.1016/j.jhep.2009.01.014 · 11.34 Impact Factor
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    ABSTRACT: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery. Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001). Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2009; 7(6):689-95. DOI:10.1016/j.cgh.2009.02.021 · 7.90 Impact Factor
  • Anne T Wolf · Rie Maurer · Jonathan Glickman · Norman D Grace
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    ABSTRACT: Liver biopsy is the gold standard for establishing cirrhosis, but may provide inadequate tissue for interpretation in some patients. The aim of this study was to determine whether the hepatic venous pressure gradient predicts the presence of cirrhosis. Patients with liver disease who had undergone hepatic venous pressure gradient measurements were identified. Clinical, laboratory, and hepatic venous pressure gradient data were collected and biopsies were staged for fibrosis. Univariable logistic regression was used to identify potential predictors of cirrhosis. Multivariable logistic regression was applied to determine adjusted odds ratios. Thirty-two patients were included. The hepatic venous pressure gradient was an independent predictor of cirrhosis. On multivariable analysis, the hepatic venous pressure gradient predicted cirrhosis, with an odds ratio of 1.46 (95% confidence interval 1.05-2.02, P=0.023). Using a cutoff of >or=6.5 mm Hg, the hepatic venous pressure gradient was 86% sensitive and 80% specific for diagnosing cirrhosis. The hepatic venous pressure gradient measurement predicts the presence of cirrhosis in patients with liver disease. Therefore, when the diagnosis of cirrhosis is in question, an elevated hepatic venous pressure gradient can support the diagnosis.
    Journal of Clinical Gastroenterology 03/2008; 42(2):199-203. DOI:10.1097/01.mcg.0000225681.45088.48 · 3.50 Impact Factor
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    ABSTRACT: Current guidelines recommend esophagogastroduodenoscopy (EGD) in patients with cirrhosis to screen for gastroesophageal varices (GEV). Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV. There is no agreement regarding a specific platelet count (PLT) that can reliably predict GEV. The present longitudinal study aims to (1) further investigate the relationship between varices and PLT at the time of endoscopy, (2) investigate whether changes in PLT from the baseline over time can predict the development of GEV, and (3) investigate whether changes in PLT correlate with the hepatic venous pressure gradient (HVPG). A secondary analysis was conducted for 213 subjects with compensated cirrhosis with portal hypertension but without GEV enrolled in a randomized, placebo-controlled, double-blind trial of a nonselective beta-blocker used to prevent GEV. PLTs were obtained every 3 months, and HVPG measurements and EGD were done annually. The PLTs were compared between subjects who did and did not develop GEV. In a median follow-up of 54.9 months, 84 patients developed GEV. PLT was greater than 150,000 in 15% of patients at the development of GEV. A receiver operating curve did not show any PLT with high sensitivity or specificity for the presence of GEV. Subjects with clinically insignificant portal hypertension (HVPG < 10 mm Hg) whose PLT remained greater than 100,000 had a 2-fold reduction in the occurrence of GEV (P = 0.0374). A significant correlation was found between HVPG and PLT at the baseline, year 1, and year 5 (P < 0.0001). Conclusion: Cross-sectional or longitudinal evaluations of PLTs are inadequate noninvasive markers for GEV. Patients with mild portal hypertension whose PLT remains greater than 100,000 have significantly less risk of GEV. Although HVPG correlates somewhat with PLT, changes in PLT cannot be used as a surrogate for HVPG changes.
    Hepatology 12/2007; 47(1):153-9. DOI:10.1002/hep.21941 · 11.06 Impact Factor
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    ABSTRACT: The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print., *2007 Journal Citation Report (Thomson Reuters, 2008)
    The American Journal of Gastroenterology 10/2007; 102(9):2086-102. DOI:10.1111/j.1572-0241.2007.01481.x · 10.76 Impact Factor
  • Norman D. Grace
    Hepatology 09/2007; 3(1):124-125. DOI:10.1002/hep.1840030120 · 11.06 Impact Factor
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    Hepatology 09/2007; 46(3):922-38. DOI:10.1002/hep.21907 · 11.06 Impact Factor
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    ABSTRACT: Our aim was to identify predictors of clinical decompensation (defined as the development of ascites, variceal hemorrhage [VH], or hepatic encephalopathy [HE]) in patients with compensated cirrhosis and with portal hypertension as determined by the hepatic venous pressure gradient (HVPG). We analyzed 213 patients with compensated cirrhosis and portal hypertension but without varices included in a trial evaluating the use of beta-blockers in preventing varices. All had baseline laboratory tests and HVPG. Patients were followed prospectively every 3 months until development of varices or VH or end of study. To have complete information, until study termination, about clinical decompensation, medical record review was done. Patients who underwent liver transplantation without decompensation were censored at transplantation. Cox regression models were developed to identify predictors of clinical decompensation. Receiver operating characteristic (ROC) curves were constructed to evaluate diagnostic capacity of HVPG. Median follow-up time of 51.1 months. Sixty-two (29%) of 213 patients developed decompensation: 46 (21.6%) ascites, 6 (3%) VH, 17 (8%) HE. Ten patients received a transplant and 12 died without clinical decompensation. Median HVPG at baseline was 11 mm Hg (range, 6-25 mm Hg). On multivariate analysis, 3 predictors of decompensation were identified: HVPG (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.05-1.17), model of end-stage liver disease (MELD) (HR, 1.15; 95% CI, 1.03-1.29), and albumin (HR, 0.37; 95% CI, 0.22-0.62). Diagnostic capacity of HVPG was greater than for MELD or Child-Pugh score. HVPG, MELD, and albumin independently predict clinical decompensation in patients with compensated cirrhosis. Patients with an HVPG <10 mm Hg have a 90% probability of not developing clinical decompensation in a median follow-up of 4 years.
    Gastroenterology 08/2007; 133(2):481-8. DOI:10.1053/j.gastro.2007.05.024 · 16.72 Impact Factor
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    Norman D Grace · Lyle B Dennis
    Hepatology 06/2007; 45(6):1337-9. DOI:10.1002/hep.21762 · 11.06 Impact Factor
  • Melissa A Minor · Norman D Grace
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    ABSTRACT: Portal hypertension is a progressively debilitating complication of cirrhosis and a principal cause of mortality in patients who have hepatic decompensation. During the last few decades, significant clinical advances in the prevention of initial variceal hemorrhage, the management of acute variceal hemorrhage, and the prevention of recurrent variceal hemorrhage have reduced the morbidity and mortality of this lethal complication of cirrhosis. This article discusses the pharmacologic treatment of portal hypertension, including preprimary prophylaxis, prevention of a first variceal hemorrhage, treatment of acute variceal hemorrhage, and secondary prophylaxis of a variceal hemorrhage.
    Clinics in Liver Disease 09/2006; 10(3):563-81, ix. DOI:10.1016/j.cld.2006.08.007 · 3.66 Impact Factor

Publication Stats

4k Citations
568.79 Total Impact Points


  • 2012–2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2002–2014
    • Brigham and Women's Hospital
      • • Center for Brain Mind Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2007–2011
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Hospital Universitari Germans Trias i Pujol
      Badalona, Catalonia, Spain
  • 1991–2007
    • Tufts University
      • Department of Medicine
      Бостон, Georgia, United States
  • 1998–2000
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1985–1997
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1984–1991
    • Lemuel Shattuck Hospital
      Jamaica Plain, Massachusetts, United States
  • 1988
    • Yale University
      New Haven, Connecticut, United States
  • 1986
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States